This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HIV patients with wasting are at increased risk of opportunistic complications and fatality. We hypothesized that augmenting dietary intake with high-biologic-value protein would enhance weight and lean tissue in weight-stable subjects with a prior unintentional weight loss of >3%. Fifty-nine subjects with HIV RNA concentrations <5000 copies/mL were randomly assigned to receive a 280-kcal supplement containing 40 g whey protein or a matched isocaloric control supplement without added protein twice daily for 12 wk. Before the study, intake of total energy and protein exceeded estimated requirements (44.3 [unreadable] 12.6 kcal/kg/d and 1.69 [unreadable] 0.55 g/kg/d, respectively). Both supplements failed to increase total energy intake because of decreases in self-selected food intake. Changes in weight (0.8 [unreadable] 2.4 and 0.7 [unreadable] 2.4 kg) and lean body mass (0.3 [unreadable] 1.4 and 0.3 [unreadable] 1.5 kg) did not differ significantly between the whey protein and control groups, respectively. Waist-to-hip ratio improved more with whey protein (-0.02 [unreadable] 0.05) than in control (0.01 [unreadable] 0.03;P=0.025) at week 6 but not at week 12. Fasting triacylglycerol increased by 39 [unreadable] 98 mg/dL with the control supplement and decreased by 16 [unreadable] 62 mg/dL with whey protein at week 12 (P=0.03). CD4 lymphocytes increased by 31 [unreadable] 84 cells/mm3 with whey protein and decreased by 5 [unreadable] 124 cells/mm3 with the control supplement at 12 wk (P=0.03). Gastrointestinal symptoms occurred more often with whey protein.